EGF-based cancer vaccine for advanced NSCLC: Results from a phase III trial.

Abstract

2527 Background: The prognosis of patients with advanced non small cell lung cancer (NSCLC) remains dismal. Epidermal Growth Factor Receptor (EGFR) is overexpressed in epithelial tumors and its role in the development of NSCLC is widely proven. The EGF vaccine is a therapeutic cancer vaccine composed by recombinant Epidermal Growth Factor (EGF) conjugated to a carrier protein, P64K from Neisseria Meningitides and Montanide, as adjuvant. The vaccine is intended to induce antibodies against self EGF that would block EGF-EGFR interaction. Methods: A multicentric, randomized Phase III trial was designed to assess the efficacy, immunogenicity and safety of the EGF cancer vaccine in advanced NSCLC patients. Patients older than 18 years with histology or cytology proven NSCLC at stage IIIB and IV were enrolled in the trial. All patients received no less than 4 platinum-based cycles and achieved at least stable disease, before entering the trial. A low-dose of cyclophosphamide was administered 3 days before the first immunization. Then, patients received 4 quarterly immunizations followed by monthly re-immunizations. Control patients received best supportive care. Results: In total, 405 patients bearing stage IIIB/IV NSCLC were recruited in 21 sites. The vaccine was very well tolerated. The most frequent adverse events consisted in grade 1/2 injection site pain, fever, headache, vomiting and chills. The vaccine was immunogenic. Antibody titers against EGF significantly increased with vaccination and on the contrary, EGF concentration in sera showed a fast reduction after immunization. There was an inverse correlation between the anti-EGF antibody titers and the EGF concentration in sera. Baseline EGF concentration was a worse prognostic factor for the control patients and a predictive factor for vaccinated subjects. The overall survival was significantly better for vaccinated patients as compared to controls. There was a direct correlation between the antibody titers and survival. Conclusions: The EGF cancer vaccine was very well tolerated and significantly increased overall survival of the vaccinated patients. Baseline EGF concentration predicted survival benefit. The EGF vaccine is a new therapeutic option for advanced NSCLC patients.